DESCRIPTION: Cell-cell signaling controls many processes in the biological world, including development, pathogenesis, mating, and transformation. Signaling processes are often mediated by factors (e. g., hormones, pheromones, neurotransmitters) that are produced by some cells and sensed by others. In bacteria, the ability to sense and respond to high population density is a type of autocrine cell-cell signaling often referred to as quorum sensing. Cells produce extracellular signaling molecules that accumulate as population density increases, and a physiological response occurs at a critical density. The long term goal of this project is to understand how quorum sensing controls gene expression and differentiation in Bacillus subtilis. We will focus on two peptide signaling factors that contribute to quorum sensing in B. subtilis: (1) ComX pheromone, a 10 amino acid peptide with a hydrophobic modification on a tryptophan, and (2) competence and sporulation stimulating factor, CSF, an unmodified pentapeptide. Both signaling molecules accumulate in culture medium as cells grow to high density and contribute to the activation (phosphorylation) of the transcription factor ComA. There are many steps required for signaling by ComX pheromone and CSF, including production of the active signaling molecules and interaction with the appropriate target molecules. CSF is transported into the cell via a the oligopeptide permease Spo0K, a member of the large family of ATP-dependent transporters, whereas ComX pheromone probably interacts with a membrane receptor histidine protein kinase ComP. We plan to address the following questions relating to both ComX pheromone and CSF: What are the determinants of biological activity? What controls production? What are the mechanisms of the response and what are the direct targets of interaction? What genes are activated by the cellular response? Our studies on quorum sensing and gene expression in this relatively simple, experimentally accessible microbe should provide insights into general mechanisms of cell-cell signaling, signal transduction, and regulation.